Nivolumab in Treating Patients With Persistent, Recurrent, or Metastatic Cervical Cancer

Cervical Adenocarcinoma Clinical Trial

Official title:

A Phase II Evaluation of Nivolumab, a Fully Human Antibody Against PD-1, in the Treatment of Persistent or Recurrent Cervical Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02257528
• Other study ID #: NCI-2014-02021
• Secondary ID: NCI-2014-02021PN
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 18, 2015
• Est. completion date: March 4, 2025

Study information

• Verified date: March 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This phase II trial studies the side effects and how well nivolumab works in treating patients with cervical cancer that has grown, come back, or spread to other places in the body. Monoclonal antibodies, such as nivolumab, may block tumor growth in different ways by targeting certain cells.

Description:

PRIMARY OBJECTIVES:

I. To assess the antitumor activity (proportion of objective response by Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 criteria) of nivolumab with objective tumor response in patients with persistent, recurrent or metastatic carcinoma of the cervix.

II. To determine the nature and degree of toxicity of nivolumab as assessed by Common Terminology Criteria for Adverse Events (CTCAE) in patients with persistent, recurrent or metastatic carcinoma of the cervix.

SECONDARY OBJECTIVES:

I. To estimate the duration of progression-free survival (PFS) and overall survival (OS).

TERTIARY OBJECTIVES:

I. To systematically evaluate programmed cell death (PD)-1 and B7 homolog 1 (B7-H1) (i.e., PD-1 ligand) expression in tumor infiltrating lymphocytes (TILs) and cervical cancer cells and explore their correlations with objective response, PFS, and OS in nivolumab-treated patients with PD-1 and B7-H1 scoring results.

II. To explore the composition of immune infiltrates in tumor specimens/biopsies from primary and/or metastatic/recurrent sites with selected markers including (but not limited) to cluster of differentiation (CD)4+, CD8+, forkhead box P3 (FoxP3), CD25, lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin mucin-3 (TIM-3), and inducible T-cell co-stimulator (ICOS) and their correlations to objective response, PFS and OS in nivolumab-treated patients.

III. To evaluate human papillomavirus (HPV) status and to explore the changes of pre- and post-immune therapy responses to HPV16/18/31/35/45 E7 antigens in patients peripheral blood lymphocytes (PBL) and serum using proliferative and interferon (IFN)-gamma enzyme-linked immunospot (ELISPOT) (cellular immunity) and serological (enzyme-linked immunosorbent assay [ELISA]) assays.

IV. To explore the levels of circulating tumor cells (CTCs) pre-treatment and at 8 and 12 weeks and their association with patient outcome.

OUTLINE:

Patients receive nivolumab intravenously (IV) over approximately 60 minutes every 2 weeks for a maximum of 46 doses over 92 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 26
• Est. completion date: March 4, 2025
• Est. primary completion date: March 5, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have persistent, recurrent or metastatic squamous cell carcinoma, adenosquamous carcinoma or adenocarcinoma of the cervix with documented disease progression (disease not amendable to curative therapy); NOTE: the following cervical tumors are not eligible: minimal deviation/adenoma malignum, gastric type adenocarcinoma, clear cell carcinoma and mesonephric carcinoma; histologic confirmation of the original primary tumor is required via the pathology report

• All patents must have measurable disease as defined by RECIST 1.1; measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded); each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic resonance imaging (MRI) or caliper measurement by clinical exam; or >= 20 mm when measured by chest x-ray; lymph nodes must be >= 15 mm in short axis when measured by CT or MRI

• Patients must have at least one "target" lesion" to be used to assess response on this protocol as defined by RECIST 1.1; tumors within a previously irradiated field will be designated as "non-target" lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy

• Appropriate for study entry based on the following diagnostic workup:

• History/physical examination within 28 days prior to registration

• Imaging of target lesion(s) within 28 days prior to registration

• Further protocol-specific assessments:

• Recovery from adverse effects of recent surgery, radiotherapy or chemotherapy

• Any other prior therapy directed at the malignant tumor including chemotherapy, biologic/targeted agents and immunologic agents must be discontinued at least three weeks prior to registration

• Investigation agents must be discontinued for at least 30 days prior to registration

• Any prior radiation therapy must be completed at least 4 weeks prior to registration

• At least 4 weeks must have elapsed since any major surgery prior to registration

• Patients must have had one prior systemic chemotherapeutic regimen for management of persistent, recurrent or metastatic carcinoma of the cervix (e.g.; paclitaxel/cisplatin, paclitaxel/cisplatin/bevacizumab); chemotherapy administered concurrent with primary radiation (e.g.; weekly cisplatin) is not counted as a systemic chemotherapy regimen; adjuvant chemotherapy given following the completion of radiation therapy (or concurrent chemotherapy and radiation therapy) is not counted as a systemic chemotherapy regimen (e.g.; paclitaxel and carboplatin for up to 4 cycles); NOTE: patients who have received more than one prior regimen are NOT eligible

• Performance status of 0 or 1

• Absolute neutrophil count (ANC) >= 1,500/ul

• Platelets >= 100,000/ul

• Creatinine =< 1.5 x institutional upper limit of normal (ULN) or creatinine clearance (CrCl) >= 40 mL/min using Cockcroft-Gault formula

• Bilirubin =< 1.5 x ULN

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN

• Normal thyroid function testing (thyroid stimulating hormone [TSH]) within 14 days prior to registration

• The patient or a legally authorized representative must provide study-specific informed consent authorization permitting release of personal health information prior to study entry

Exclusion Criteria:

• Patients who have had prior therapy with nivolumab or with an anti-PD-1, anti-PD-ligand (L)1, anti-PD-L2, anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune check point pathways

• History of severe hypersensitivity reaction to any monoclonal antibody

• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years

• Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure and unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements

• Patients who are pregnant or nursing; women of child-bearing potential (WOCBP) must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; WOCBP should use an adequate method to avoid pregnancy for 23 weeks after the last dose of investigational drug; WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IV/L or equivalent units of human chorionic gonadotropin [HCG]) within 24 hours prior to the start of nivolumab; women must not be breastfeeding

• Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile or have undergone definitive radiation) do not require contraception

• Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy of bilateral oophorectomy) or who is not postmenopausal; menopause is defined clinically as 12 month amenorrhea in a woman over 45 in the absence of other biological or physiological causes; in addition, women under the age of 55 must have a documented serum follicle stimulating hormone (FSH) level greater than 40 mIU/mL

• WOCBP receiving nivolumab will be instructed to adhere to contraception for a period of 23 weeks after the last dose of investigational product

• Should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform the treating physician immediately

• Patients with known brain metastases or leptomeningeal metastases are excluded unless the following conditions are met:

• Metastases have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for at least 4 weeks after treatment is complete (must be confirmed within 28 days prior to the first dose of nivolumab administration)

• There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration

• Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)

• Patients should be excluded if they have a positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection

• Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including systemic corticosteroids, should be excluded; these include but are not limited to patients with a history of immune related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), connective tissue diseases, scleroderma, inflammatory bowel disease (IRB), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded; patient with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible; patients with rheumatoid arthritis and other arthropathies, Sjogren's syndrome and psoriasis controlled with topical medication and patients with positive serology, such as antinuclear antibodies (ANA), anti-thyroid antibodies should be evaluated for the presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible

• NOTE: patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event)

• Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration; inhaled or topical steroids and adrenal replacement doses =< 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease; patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption); physiologic replacement doses of systemic corticosteroids are permitted, even if =< 10 mg/day prednisone equivalents; a brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted

• Patients who have had evidence of active or acute diverticulitis, intra-abdominal abscess, abdominal/pelvic fistula, gastrointestinal perforation, gastrointestinal (GI) obstruction and/or who require parenteral hydration and/or nutrition

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Adenosquamous
• Cervical Adenocarcinoma
• Cervical Adenosquamous Carcinoma
• Recurrence
• Recurrent Cervical Carcinoma
• Stage IV Cervical Cancer AJCC v6 and v7
• Stage IVA Cervical Cancer AJCC v6 and v7
• Stage IVB Cervical Cancer AJCC v6 and v7
• Uterine Cervical Neoplasms

Intervention

Other:
• Laboratory Biomarker Analysis
Correlative studies

Biological:
• Nivolumab
Given IV

Locations

Country	Name	City	State
United States	Providence Regional Cancer System-Aberdeen	Aberdeen	Washington
United States	Jefferson Abington Hospital	Abington	Pennsylvania
United States	Southwest Gynecologic Oncology Associates Inc	Albuquerque	New Mexico
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Lehigh Valley Hospital-Cedar Crest	Allentown	Pennsylvania
United States	Community Hospital of Anaconda	Anaconda	Montana
United States	Cancer Care Center at Island Hospital	Anacortes	Washington
United States	Alaska Breast Care and Surgery LLC	Anchorage	Alaska
United States	Alaska Oncology and Hematology LLC	Anchorage	Alaska
United States	Alaska Regional Hospital	Anchorage	Alaska
United States	Alaska Women's Cancer Care	Anchorage	Alaska
United States	Anchorage Associates in Radiation Medicine	Anchorage	Alaska
United States	Anchorage Oncology Centre	Anchorage	Alaska
United States	Anchorage Radiation Therapy Center	Anchorage	Alaska
United States	Katmai Oncology Group	Anchorage	Alaska
United States	Providence Alaska Medical Center	Anchorage	Alaska
United States	Sutter Auburn Faith Hospital	Auburn	California
United States	Sutter Cancer Centers Radiation Oncology Services-Auburn	Auburn	California
United States	Kaiser Permanente-Baldwin Park	Baldwin Park	California
United States	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland
United States	Flaget Memorial Hospital	Bardstown	Kentucky
United States	UHHS-Chagrin Highlands Medical Center	Beachwood	Ohio
United States	Swedish Cancer Institute-Eastside Oncology Hematology	Bellevue	Washington
United States	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington
United States	Strecker Cancer Center-Belpre	Belpre	Ohio
United States	Saint Charles Health System	Bend	Oregon
United States	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California
United States	Lehigh Valley Hospital - Muhlenberg	Bethlehem	Pennsylvania
United States	Billings Clinic Cancer Center	Billings	Montana
United States	Saint Vincent Healthcare	Billings	Montana
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	OSF Saint Joseph Medical Center	Bloomington	Illinois
United States	Prisma Health Cancer Institute - Spartanburg	Boiling Springs	South Carolina
United States	Saint Luke's Cancer Institute - Boise	Boise	Idaho
United States	Central Care Cancer Center - Bolivar	Bolivar	Missouri
United States	Parkland Health Center-Bonne Terre	Bonne Terre	Missouri
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital Cancer Center	Boston	Massachusetts
United States	Bozeman Health Deaconess Hospital	Bozeman	Montana
United States	Cox Cancer Center Branson	Branson	Missouri
United States	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington
United States	Henry Ford Cancer Institute-Downriver	Brownstown	Michigan
United States	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California
United States	Highline Medical Center-Main Campus	Burien	Washington
United States	Mills-Peninsula Medical Center	Burlingame	California
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana
United States	Cooper Hospital University Medical Center	Camden	New Jersey
United States	Sutter Cancer Centers Radiation Oncology Services-Cameron Park	Cameron Park	California
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Cancer Center	Cape Girardeau	Missouri
United States	Memorial Hospital of Carbondale	Carbondale	Illinois
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Eden Hospital Medical Center	Castro Valley	California
United States	Dayton Physicians LLC-Miami Valley South	Centerville	Ohio
United States	Miami Valley Hospital South	Centerville	Ohio
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	Providence Regional Cancer System-Centralia	Centralia	Washington
United States	Christiana Care Health System-Concord Health Center	Chadds Ford	Pennsylvania
United States	Cancer Center of Kansas - Chanute	Chanute	Kansas
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Memorial Hospital	Chattanooga	Tennessee
United States	Northwestern University	Chicago	Illinois
United States	Adena Regional Medical Center	Chillicothe	Ohio
United States	Bethesda North Hospital	Cincinnati	Ohio
United States	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio
United States	Oncology Hematology Care Inc-Kenwood	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Anderson	Cincinnati	Ohio
United States	TriHealth Cancer Institute-Westside	Cincinnati	Ohio
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon
United States	Case Western Reserve University	Cleveland	Ohio
United States	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	Sampson Radiation Oncology	Clinton	North Carolina
United States	Southeastern Medical Oncology Center-Clinton	Clinton	North Carolina
United States	Henry Ford Macomb Hospital-Clinton Township	Clinton Township	Michigan
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Mission Cancer and Blood - West Des Moines	Clive	Iowa
United States	Big Horn Basin Cancer Center	Cody	Wyoming
United States	Billings Clinic-Cody	Cody	Wyoming
United States	Kootenai Health - Coeur d'Alene	Coeur d'Alene	Idaho
United States	Columbus Oncology and Hematology Associates Inc	Columbus	Ohio
United States	Doctors Hospital	Columbus	Ohio
United States	Grant Medical Center	Columbus	Ohio
United States	Mount Carmel East Hospital	Columbus	Ohio
United States	Mount Carmel Health Center West	Columbus	Ohio
United States	Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	Riverside Methodist Hospital	Columbus	Ohio
United States	The Mark H Zangmeister Center	Columbus	Ohio
United States	Bay Area Hospital	Coos Bay	Oregon
United States	Commonwealth Cancer Center-Corbin	Corbin	Kentucky
United States	Alegent Health Mercy Hospital	Council Bluffs	Iowa
United States	Greater Regional Medical Center	Creston	Iowa
United States	Sutter Davis Hospital	Davis	California
United States	Dayton Physician LLC - Englewood	Dayton	Ohio
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Miami Valley Hospital North	Dayton	Ohio
United States	Henry Ford Medical Center-Fairlane	Dearborn	Michigan
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Delaware Health Center-Grady Cancer Center	Delaware	Ohio
United States	Delaware Radiation Oncology	Delaware	Ohio
United States	Grady Memorial Hospital	Delaware	Ohio
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Laurel	Des Moines	Iowa
United States	Henry Ford Hospital	Detroit	Michigan
United States	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan
United States	Cancer Center of Kansas - Dodge City	Dodge City	Kansas
United States	Prisma Health Cancer Institute - Easley	Easley	South Carolina
United States	Swedish Cancer Institute-Edmonds	Edmonds	Washington
United States	Crossroads Cancer Center	Effingham	Illinois
United States	Cancer Center of Kansas - El Dorado	El Dorado	Kansas
United States	Saint Elizabeth Hospital	Enumclaw	Washington
United States	Ephrata Cancer Center	Ephrata	Pennsylvania
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Providence Regional Cancer Partnership	Everett	Washington
United States	Inova Fairfax Hospital	Falls Church	Virginia
United States	Weisberg Cancer Treatment Center	Farmington Hills	Michigan
United States	Saint Francis Hospital	Federal Way	Washington
United States	Armes Family Cancer Center	Findlay	Ohio
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Orion Cancer Care	Findlay	Ohio
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Dayton Physicians LLC-Atrium	Franklin	Ohio
United States	Saint Luke's Cancer Institute - Fruitland	Fruitland	Idaho
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Western Illinois Cancer Treatment Center	Galesburg	Illinois
United States	Adams Cancer Center	Gettysburg	Pennsylvania
United States	Southeastern Medical Oncology Center-Goldsboro	Goldsboro	North Carolina
United States	Wayne Memorial Hospital	Goldsboro	North Carolina
United States	Wayne Radiation Oncology	Goldsboro	North Carolina
United States	Nebraska Cancer Specialists/Oncology Hematology West PC	Grand Island	Nebraska
United States	Benefis Sletten Cancer Institute	Great Falls	Montana
United States	Great Falls Clinic	Great Falls	Montana
United States	Dayton Physicians LLC-Wayne	Greenville	Ohio
United States	Greenville Health System Cancer Institute-Andrews	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina
United States	Prisma Health Cancer Institute - Faris	Greenville	South Carolina
United States	Prisma Health Greenville Memorial Hospital	Greenville	South Carolina
United States	Saint Francis Cancer Center	Greenville	South Carolina
United States	Saint Francis Hospital	Greenville	South Carolina
United States	Wayne Hospital	Greenville	Ohio
United States	Prisma Health Cancer Institute - Greer	Greer	South Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	WellSpan Medical Oncology and Hematology	Hanover	Pennsylvania
United States	Saint Peter's Community Hospital	Helena	Montana
United States	Sudarshan K Sharma MD Limited-Gynecologic Oncology	Hinsdale	Illinois
United States	Pulmonary Medicine Center of Chattanooga-Hixson	Hixson	Tennessee
United States	CHI Saint Vincent Cancer Center Hot Springs	Hot Springs	Arkansas
United States	M D Anderson Cancer Center	Houston	Texas
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Indiana University/Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	Sidney and Lois Eskenazi Hospital	Indianapolis	Indiana
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Swedish Cancer Institute-Issaquah	Issaquah	Washington
United States	Onslow Memorial Hospital	Jacksonville	North Carolina
United States	Southeastern Medical Oncology Center-Jacksonville	Jacksonville	North Carolina
United States	MU Health Care Goldschmidt Cancer Center	Jefferson City	Missouri
United States	Freeman Health System	Joplin	Missouri
United States	Mercy Hospital Joplin	Joplin	Missouri
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	CHI Health Good Samaritan	Kearney	Nebraska
United States	Heartland Hematology and Oncology	Kearney	Nebraska
United States	Greater Dayton Cancer Center	Kettering	Ohio
United States	Kettering Medical Center	Kettering	Ohio
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Cancer Center of Kansas-Kingman	Kingman	Kansas
United States	UC San Diego Moores Cancer Center	La Jolla	California
United States	Providence Regional Cancer System-Lacey	Lacey	Washington
United States	Saint Clare Hospital	Lakewood	Washington
United States	Fairfield Medical Center	Lancaster	Ohio
United States	Women's Cancer Center of Nevada	Las Vegas	Nevada
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Beebe Medical Center	Lewes	Delaware
United States	Saint Joseph Hospital East	Lexington	Kentucky
United States	Saint Joseph Radiation Oncology Resource Center	Lexington	Kentucky
United States	Cancer Center of Kansas-Liberal	Liberal	Kansas
United States	Saint Elizabeth Regional Medical Center	Lincoln	Nebraska
United States	PeaceHealth Saint John Medical Center	Longview	Washington
United States	Jewish Hospital	Louisville	Kentucky
United States	Saints Mary and Elizabeth Hospital	Louisville	Kentucky
United States	UofL Health Medical Center Northeast	Louisville	Kentucky
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Marietta Memorial Hospital	Marietta	Ohio
United States	OhioHealth Marion General Hospital	Marion	Ohio
United States	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio
United States	UH Seidman Cancer Center at Landerbrook Health Center	Mayfield Heights	Ohio
United States	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio
United States	Saint Luke's Cancer Institute - Meridian	Meridian	Idaho
United States	Dayton Physicians LLC-Signal Point	Middletown	Ohio
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Community Medical Center	Missoula	Montana
United States	Saint Patrick Hospital - Community Hospital	Missoula	Montana
United States	Memorial Medical Center	Modesto	California
United States	Monongalia Hospital	Morgantown	West Virginia
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Knox Community Hospital	Mount Vernon	Ohio
United States	Palo Alto Medical Foundation-Camino Division	Mountain View	California
United States	Palo Alto Medical Foundation-Gynecologic Oncology	Mountain View	California
United States	Saint Luke's Cancer Institute - Nampa	Nampa	Idaho
United States	Yale University	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
United States	Christiana Gynecologic Oncology LLC	Newark	Delaware
United States	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware
United States	Helen F Graham Cancer Center	Newark	Delaware
United States	Licking Memorial Hospital	Newark	Ohio
United States	Medical Oncology Hematology Consultants PA	Newark	Delaware
United States	Newark Radiation Oncology	Newark	Ohio
United States	Providence Newberg Medical Center	Newberg	Oregon
United States	Cancer Center of Kansas - Newton	Newton	Kansas
United States	Henry Ford Medical Center-Columbus	Novi	Michigan
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska
United States	Alegent Health Immanuel Medical Center	Omaha	Nebraska
United States	Alegent Health Lakeside Hospital	Omaha	Nebraska
United States	Creighton University Medical Center	Omaha	Nebraska
United States	Hematology and Oncology Consultants PC	Omaha	Nebraska
United States	Memorial GYN Plus	Ooltewah	Tennessee
United States	Providence Willamette Falls Medical Center	Oregon City	Oregon
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Radiation Oncology of Northern Illinois	Ottawa	Illinois
United States	Palo Alto Medical Foundation Health Care	Palo Alto	California
United States	Midlands Community Hospital	Papillion	Nebraska
United States	Cancer Center of Kansas - Parsons	Parsons	Kansas
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	OSF Saint Francis Radiation Oncology at Pekin	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	OSF Saint Francis Radiation Oncology at Peoria Cancer Center	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Valley Radiation Oncology	Peru	Illinois
United States	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Southern Ohio Medical Center	Portsmouth	Ohio
United States	Kootenai Clinic Cancer Services - Post Falls	Post Falls	Idaho
United States	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington
United States	Cancer Center of Kansas - Pratt	Pratt	Kansas
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Women and Infants Hospital	Providence	Rhode Island
United States	Beebe Health Campus	Rehoboth Beach	Delaware
United States	Reid Health	Richmond	Indiana
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	Sutter Cancer Centers Radiation Oncology Services-Roseville	Roseville	California
United States	Sutter Roseville Medical Center	Roseville	California
United States	Sutter Medical Center Sacramento	Sacramento	California
United States	Mercy Hospital Saint Louis	Saint Louis	Missouri
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri
United States	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	Cancer Center of Kansas - Salina	Salina	Kansas
United States	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah
United States	Kaiser Permanente-San Diego Mission	San Diego	California
United States	Kaiser Permanente-San Diego Zion	San Diego	California
United States	California Pacific Medical Center-Pacific Campus	San Francisco	California
United States	Kaiser Permanente-San Marcos	San Marcos	California
United States	Kootenai Clinic Cancer Services - Sandpoint	Sandpoint	Idaho
United States	Palo Alto Medical Foundation-Santa Cruz	Santa Cruz	California
United States	Sutter Pacific Medical Foundation	Santa Rosa	California
United States	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia
United States	Low Country Cancer Care	Savannah	Georgia
United States	Memorial Health University Medical Center	Savannah	Georgia
United States	Summit Cancer Care-Memorial	Savannah	Georgia
United States	Maine Medical Center- Scarborough Campus	Scarborough	Maine
United States	TidalHealth Nanticoke / Allen Cancer Center	Seaford	Delaware
United States	FHCC South Lake Union	Seattle	Washington
United States	Fred Hutchinson Cancer Center	Seattle	Washington
United States	Kaiser Permanente Washington	Seattle	Washington
United States	Minor and James Medical PLLC	Seattle	Washington
United States	Pacific Gynecology Specialists	Seattle	Washington
United States	Swedish Medical Center-Ballard Campus	Seattle	Washington
United States	Swedish Medical Center-First Hill	Seattle	Washington
United States	University of Washington Medical Center - Montlake	Seattle	Washington
United States	University of Washington Medical Center - Northwest	Seattle	Washington
United States	Women's Cancer Center of Seattle	Seattle	Washington
United States	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina
United States	Providence Regional Cancer System-Shelton	Shelton	Washington
United States	Jewish Hospital Medical Center South	Shepherdsville	Kentucky
United States	Welch Cancer Center	Sheridan	Wyoming
United States	Dayton Physicians LLC-Wilson	Sidney	Ohio
United States	Saint Michael Cancer Center	Silverdale	Washington
United States	Avera Cancer Institute	Sioux Falls	South Dakota
United States	South Jordan Health Center	South Jordan	Utah
United States	Evergreen Hematology and Oncology PS	Spokane	Washington
United States	MultiCare Deaconess Cancer and Blood Specialty Center - Downtown	Spokane	Washington
United States	MultiCare Deaconess Cancer and Blood Specialty Center - Valley	Spokane Valley	Washington
United States	Central Illinois Hematology Oncology Center	Springfield	Illinois
United States	CoxHealth South Hospital	Springfield	Missouri
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Springfield Regional Cancer Center	Springfield	Ohio
United States	Springfield Regional Medical Center	Springfield	Ohio
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	Palo Alto Medical Foundation-Sunnyvale	Sunnyvale	California
United States	BJC Outpatient Center at Sunset Hills	Sunset Hills	Missouri
United States	Franciscan Research Center-Northwest Medical Plaza	Tacoma	Washington
United States	Northwest Medical Specialties PLLC	Tacoma	Washington
United States	Dayton Physicians LLC - Troy	Troy	Ohio
United States	Upper Valley Medical Center	Troy	Ohio
United States	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma
United States	Saint Luke's Cancer Institute - Twin Falls	Twin Falls	Idaho
United States	Sutter Cancer Centers Radiation Oncology Services-Vacaville	Vacaville	California
United States	Sutter Solano Medical Center/Cancer Center	Vallejo	California
United States	PeaceHealth Southwest Medical Center	Vancouver	Washington
United States	MD Anderson Cancer Center at Cooper-Voorhees	Voorhees	New Jersey
United States	University Hospitals Sharon Health Center	Wadsworth	Ohio
United States	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington
United States	Cancer Center of Kansas - Wellington	Wellington	Kansas
United States	Henry Ford West Bloomfield Hospital	West Bloomfield	Michigan
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Reading Hospital	West Reading	Pennsylvania
United States	Saint Ann's Hospital	Westerville	Ohio
United States	UHHS-Westlake Medical Center	Westlake	Ohio
United States	Ascension Via Christi Hospitals Wichita	Wichita	Kansas
United States	Associates In Womens Health	Wichita	Kansas
United States	Cancer Center of Kansas - Wichita	Wichita	Kansas
United States	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas
United States	Christiana Care Health System-Wilmington Hospital	Wilmington	Delaware
United States	Cancer Center of Kansas - Winfield	Winfield	Kansas
United States	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington
United States	Providence Regional Cancer System-Yelm	Yelm	Washington
United States	WellSpan Health-York Cancer Center	York	Pennsylvania
United States	WellSpan Health-York Hospital	York	Pennsylvania
United States	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)	NRG Oncology

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Tumor Expressions of PD-1 and PD-L1 in Tumor Infiltrating Lymphocytes and Cervical Cancer Cells	Spearman's correlation coefficient will be used to explore the associations of tumor expressions of PD-L1, PD-1 and other interested biomarkers with tumor response. Cox proportional hazards (PH) model will be utilized to evaluate the associations of these tumor expressions with PFS and OS. These expressions may also be dichotomized into high versus low values (cut at the median). Log-rank tests will be used to assess the associations of these dichotomized tumor expressions with PFS and OS. The corresponding hazard rations will be estimated by Cox PH models.	Up to 5 years
Other	Immune Infiltration Related Biomarkers (i.e., CD4+, CD8+, FoxP3) in Tumor Specimens	Immune infiltration related biomarkers (i.e., CD4+, CD8+, FoxP3) in tumor specimens will be associated with objective tumor response, PFS and OS in nivolumab-treated patients.	Up to 5 years
Other	Change in the Immune Response to HPV 16/18/31/35/45 E7 Antigen in Peripheral Blood Lymphocytes and Serum	Wilcoxon signed rank test (for interval or ordinal data) or McNemar's test (for binary data) may be utilized to examine whether the study treatment will change immune response to HPV 16/18/31/35/45 E7 antigen in peripheral blood lymphocytes and serum by changes in the measures of pre- and post-treatment immune response to HPV 16/18/31/35/45 E7.	Baseline to up to 5 years
Other	Change in the CTC Count	Change in the CTC count and whether the CTC count is associated with objective response, PFS and OS in nivolumab-treated patients will be evaluated.	Baseline to up to 12 weeks
Primary	Objective Tumor Response as Assessed by RECIST 1.1 Criteria	Proportion of participants with objective tumor response. Objective tumor response is defined as complete or partial tumor response assessed by RECIST 1.1.	The average of study treatment time was 3.8 months.
Primary	Adverse Events (Grade 3 or Higher) During Treatment Period as Assessed by CTCAE Version 4	Number of participants with a maximum grade of 3 or higher during treatment period. Adverse events are graded and categorized using CTCAE v4.0.	Within 100 days of last protocol treatment
Secondary	Progression-free Survival	Progression-free survival is the period of time from study entry to time of disease progression, death or date of last contact, whichever occurs first. Progression is assessed by RECIST 1.1.	Time from study entry to time of progression or death, whichever occurs first, up to 5 years of follow-up.
Secondary	Overall Survival	Overall survival is defined as the duration of time from study entry to time of death or the date of last contact.	Time from study entry to time of death or the date of last contact, up to 5 years of follow-up